AB0004 PTPN22 AND TNFAIP3, BUT NOT STAT4, ARE RISK FACTORS FOR IGG4-RELATED DISEASE
Authors: E. Martin-Nares, G. Hernandez-Molina, J. Ramírez Bello
Journal: Annals of the Rheumatic Diseases (2022)

Background The etiology of IgG4-related disease (IgG4-RD) is not yet clear, but environmental and genetic factors are thought to be involved. Little is known about the genes that confer susceptibility to this disease, which is why various loci related to inflammation or autoimmunity have begun to be studied. Such studies are limited to Asian and European cohorts. To date, no study has searched susceptibility genes for the development of IgG4-RD in the Mexican Mestizo population. Objectives To determine whether three single nucleotide variants (SNVs) located in classic genes associated with systemic lupus erythematosus and rheumatoid arthritis, namely, TNFAIP3 (rs2330926T/G), STAT4 (rs7574865G/T), and PTPN22 (rs2476601C/T), confer susceptibility for the development of IgG4-RD in the Mexican Mestizo population. Methods Patients who met the 2019 ACR/EULAR classification criteria for IgG4-RD were included. For each patient, two healthy controls were matched by sex who had no history of chronic, inflammatory, or autoimmune diseases. Both patients and controls were unrelated and self-reported with Mexican Mestizo ancestry by linage (at least three generations including their own). Genomic DNA was extracted from peripheral blood cells. SNVs were genotyped using TaqMan probes and the 5’ exonuclease assay. The Chi-square test was used to determine odds ratios. Results We included 124 controls and 60 patients with IgG4-RD (31 (51.6%) female and 29 (48.4%) male). Patients with IgG4-RD had a mean age of 52.1 ±15 years. Ten (16.6%) had single organ involvement, 10 (16.7%) had two involved organs, and 40 (66.6%) had ≥ 3 involved organs. Thirteen (21.7%) belonged to the pancreato-hepato-biliary, 5 (8.3%) to the retroperitoneal/aortic, 19 (31.7%) to the head/neck-limited, 18 (30%) to the Mikulicz/systemic, and 5 (8.3) to the undetermined phenotype, while 43 (71.7%) belonged to the proliferative and 17 (28.3%) to the fibrotic phenotypes. The allelic and genotypic frequencies of the SNV rs7574865G/T of STAT4 did not show statistically significant differences between cases and controls ( p &gt;0.05); while the PTPN22 variant rs2476601C/T showed association with IgG4-RD: allele C vs T, OR 10.6, CI 95% 1.22 - 91.37, p =0.02 and CC vs CT, OR 11.0, CI 95% 1.25 - 96.2, p =0.008; and the SNV rs2230296T/G of TNFAIP3 showed the following association: T vs G, OR 2.8, 1.03 - 7.87, p =0.04 and TT vs TG, OR 3.0, 95% CI 1.07 -8.60, p =0.03. Conclusion This is the first study to suggest that the STAT4 variant rs7574865G/G is not a risk factor for the development of IgG4-RD, while the variants rs2476601C/T of PTPN22 and rs2230936T/G of TNFAIP3 confer susceptibility to the development of this disease in the Mexican Mestizo population. Our study provides new information on the genetic basis of IgG4-RD. References [1]Buechter M, Manka P, Heinemann FM et al. Outcome and Genetic Factors in IgG4-Associated Autoimmune Pancreatitis and Cholangitis: A Single Center Experience. Gastroenterol Res Pract. 2017;2017:6126707. [2]Terao C, Ota M, Iwasaki T, et al. IgG4-related disease in the Japanese population: a genome-wide association study. Lancet Rheumatol 2019;1:e14-22. doi:10.1016/S2665-9913(19)30006-2 Disclosure of Interests None declared